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Condition: Cystic Fibrosis

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Total 62 results found since Jan 2013.

siRNA delivery to macrophages using aspherical, nanostructured microparticles as delivery system for pulmonary administration.
Abstract The delivery of oligonucleotides such as siRNA to the lung is a major challenge, as this group of drugs has difficulties to overcome biological barriers due to its polyanionic character and the associated hydrophilic properties, resulting in inefficient delivery. Especially in diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis, where increased proinflammation is present, a targeted RNA therapy is desirable due to the high potency of these oligonucleotides. To address these problems and to ensure efficient uptake of siRNA in macrophages, a microparticulate, cylindrical deliv...
Source: European Journal of Pharmaceutics and Biopharmaceutics - December 4, 2020 Category: Drugs & Pharmacology Authors: Fischer T, Tschernig T, Drews F, Brix K, Meier C, Simon M, Kautenburger R, Schneider M Tags: Eur J Pharm Biopharm Source Type: research

Spray drying siRNA-lipid nanoparticles for dry powder pulmonary delivery
This study verifies the successful spray drying procedure of LNP-siRNA systems maintaining their integrity and mediating strong gene silencing efficiency on mRNA and protein levels both in vitro and ex vivo. The successful spray drying procedure of LNP-siRNA formulations in 5% lactose solution creates a novel siRNA-based therapy option to target respiratory diseases such as lung cancer, asthma, COPD, cystic fibrosis and viral infections.PMID:36126785 | DOI:10.1016/j.jconrel.2022.09.021
Source: Cancer Control - September 20, 2022 Category: Cancer & Oncology Authors: Christoph M Zimmermann Domizia Baldassi Karen Chan Nathan B P Adams Alina Neumann Diana Leidy Porras-Gonzalez Xin Wei Nikolaus Kneidinger Mircea Gabriel Stoleriu Gerald Burgstaller Dominik Witzigmann Paola Luciani Olivia M Merkel Source Type: research

Genes, Vol. 11, Pages 351: Extracellular Vesicle-Mediated siRNA Delivery, Protein Delivery, and CFTR Complementation in Well-Differentiated Human Airway Epithelial Cells
L. Sinn Extracellular vesicles (EVs) are a class of naturally occurring secreted cellular bodies that are involved in long distance cell-to-cell communication. Proteins, lipids, mRNA, and miRNA can be packaged into these vesicles and released from the cell. This information is then delivered to target cells. Since EVs are naturally adapted molecular messengers, they have emerged as an innovative, inexpensive, and robust method to deliver therapeutic cargo in vitro and in vivo. Well-differentiated primary cultures of human airway epithelial cells (HAE) are refractory to standard transfection techniques. Indeed, common s...
Source: Genes - March 25, 2020 Category: Genetics & Stem Cells Authors: Brajesh K. Singh Ashley L. Cooney Sateesh Krishnamurthy Patrick L. Sinn Tags: Article Source Type: research

Induction of heme oxygenase-1 contributes to survival of Mycobacterium abscessus in human macrophages-like THP-1 cells
Publication date: Available online 20 January 2015 Source:Redox Biology Author(s): Maher Y. Abdalla , Iman M. Ahmad , Barbara Switzer , Bradley E. Britigan Mycobacterium abscessus (M.abs) is a rapidly growing mycobacterial species that infects macrophages, and is an important pathogen in patients with cystic fibrosis. We studied the early stages of M.abs infection of macrophages, with emphasis on the role of heme-oxygenase-1 (HO-1) in this infection. THP-1 cells were activated using TPA into macrophage-like cells and infected with M.abs for different time points. M.abs infection robustly induced HO-1 expression in the TH...
Source: Redox Biology - January 23, 2015 Category: Biology Source Type: research

Pro-resolving Action of MAG-DHA in Lung Inflammatory Models Related to Cystic Fibrosis.
CONCLUSIONS: MAG-DHA displays anti-inflammatory properties and reduces mucin overexpression in Calu-3 cells and human bronchi untreated or treated with P. aeruginosa LPS, a finding consistent with the effects of ResolvinD1, a known anti-inflammatory mediator. PMID: 25781052 [PubMed - as supplied by publisher]
Source: Am J Respir Cell Mol... - March 17, 2015 Category: Respiratory Medicine Authors: Morin C, Cantin AM, Rousseau É, Sirois M, Sirois C, Rizcallah E, Fortin S Tags: Am J Respir Cell Mol Biol Source Type: research

Chitosan as a non-viral co-transfection system in a cystic fibrosis cell line
This study shows proof-of-principle that co-transfection with chitosan might be an effective delivery system in a human CF cell line. It also offers a potential alternative to further develop therapeutic strategies for inherited disease treatments, such as CF. Graphical abstract
Source: International Journal of Pharmaceutics - February 22, 2016 Category: Drugs & Pharmacology Source Type: research

Immune-Modulation by the Human Respiratory Syncytial Virus: Focus on Dendritic Cells
This study is complemented by another report that found that hRSV infection induces significant expression of three miRNAs, namely hsa-miR-4448, hsa-miR-30a-5p, and hsa-miR-4634 in human DCs (104). Interestingly, this latter study also performed comparative analyses of miRNA profiles between DCs infected with hRSV and a related virus, namely the human metapneumovirus, and found that both viruses induced the expression of elevated levels of hsa-miR-4634. Elucidating the contribution of these miRNAs in DCs in response to hRSV remains to be determined. Dendritic Cell Phenotype and Migration Upon hRSV Infection in vivo Altho...
Source: Frontiers in Immunology - April 14, 2019 Category: Allergy & Immunology Source Type: research

Efficient Delivery of RNA-interference Oligonucleotides to Polarized Airway Epithelia In Vitro.
Abstract Polarized and pseudostratified primary airway epithelia present barriers that significantly reduce their transfection efficiency and the efficacy of RNA-interference oligonucleotides. This creates an impediment in studies of the airway epithelium, diminishing the utility of loss-of-function as a research tool. Here we outline methods to introduce RNA interference (RNAi) oligonucleotides into primary human and porcine airway epithelia grown at an air-liquid interface and difficult to transfect transformed epithelial cell lines grown on plastic. At the time of plating, we reverse transfect small-interfering...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - April 26, 2013 Category: Cytology Authors: Ramachandran S, Krishnamurthy S, Jacobi AM, Wohlford-Lenane C, Behlke MA, Davidson BL, McCray PB Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research

A functional tandem between transient receptor potential canonical channels 6 and calcium-dependent chloride channels in Human epithelial cells.
In conclusion, we show that TRPC6 channel is pivotal for the activation of CaCC by guanabenz through a α2-adrenergic-independent pathway in human airway epithelial cells. We suggest propose a functional coupling between TRPC6 and CaCC and guanabenz as a potential TRPC6 activator for exploring TRPC6 and CaCC channel functions and corresponding channelopathies. PMID: 26265544 [PubMed - as supplied by publisher]
Source: European Journal of Pharmacology - August 8, 2015 Category: Drugs & Pharmacology Authors: Bertrand J, Dannhoffer L, Antigny F, Vachel L, Jayle C, Vandebrouck C, Becq F, Norez C Tags: Eur J Pharmacol Source Type: research

From Genesis To Revelation: The Role Of Inflammatory Mediators In Chronic Respiratory Diseases And Their Control By Nucleic Acid-Based Drugs.
Abstract Asthma, chronic obstructive pulmonary disease, cystic fibrosis, and idiopathic pulmonary fibrosis, are among the most common chronic diseases and their prevalence is increasing. Each of these diseases is characterized by the secretion of cytokines and pro-inflammatory molecules which are thought to play a critical role in their pathogenesis. Moreover, immune cells, particularly neutrophils, macrophages and dendritic cells as well structural cells such as epithelial and airway smooth muscle cells are also involved in the pathogenic cycle of these diseases. There is a pressing need for the development of ne...
Source: Current Drug Delivery - August 23, 2016 Category: Drugs & Pharmacology Authors: Di Gioia S, Sardo C, Castellani S, Porsio B, Belgiovine G, Carbone A, Giammona G, Cavallaro G Tags: Curr Drug Deliv Source Type: research

Cellular mechanism for herbal medicine Junchoto to facilitate intestinal Cl − /water secretion that involves cAMP-dependent activation of CFTR
AbstractConstipation is a common symptom frequently compromising the quality of daily life. Several mechanistically different drugs have been used to mitigate constipation, including Japanese herbal (Kampo) medicines. However, the mechanisms of their actions are often not well understood. Here we aimed to investigate the molecular mechanisms underlying the effects of Junchoto (JCT), a Kampo medicine empirically prescribed for chronic constipation. Cl− channel activity was measured by the patch-clamp method in human cystic fibrosis transmembrane conductance regulator (CFTR)-expressing HEK293T cells and human intestinal Ca...
Source: Journal of Natural Medicines - March 22, 2018 Category: Drugs & Pharmacology Source Type: research

B-Cell Receptor-Associated Protein 31 Regulates the Expression of Valosin-Containing Protein Through Elf2
Conclusion: These results indicate that Bap31 regulates the expression of VCP possibly via Elf2 and support the potential molecular function of Bap31 in CNS diseases.Cell Physiol Biochem 2018;51:1799 –1814
Source: Cellular Physiology and Biochemistry - November 30, 2018 Category: Cytology Source Type: research

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in Human Lung Microvascular Endothelial Cells Controls Oxidative Stress, Reactive Oxygen-Mediated Cell Signaling and Inflammatory Responses
ConclusionFunctional endothelial CFTR limits oxidative stress and contributes to the normal anti-inflammatory state of HLMVECs. Therapeutic strategies to restore endothelial CFTR function in CF are warranted.
Source: Frontiers in Physiology - July 28, 2020 Category: Physiology Source Type: research

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Plays an Important Role in Fetal Human Colon Cell Migration and Proliferation
CONCLUSION-: Our results indicate that CFTR plays an important role in FHC colon cell migration and EGFR signaling, which could lead to a better understanding as to why CF patients have increased risk for colon cancer.PMID:35556394 | DOI:10.1096/fasebj.2022.36.S1.R6139
Source: Cancer Control - May 13, 2022 Category: Cancer & Oncology Authors: Cara A Mogan Garett J Grant Kaylee LeBaron Theodore G Liou My N Helms Source Type: research

Tartrate resistant acid phosphatase 5 (TRAP5) mediates immune cell recruitment in a murine model of pulmonary bacterial infection
In this study, we found that Trap5-/- mice had impaired clearance of P. aeruginosa airway infection and reduced recruitment of immune cells (i.e. neutrophils and inflammatory macrophages). Trap5 knockdown using siRNA resulted in a decreased activation of the proinflammatory transcription factor NF-κB in reporter mice and a subsequent decrease of proinflammatory gene expression. Add-back experiments of enzymatically active TRAP5 to Trap5-/- mice restored immune cell recruitment and bacterial killing. In human CF lung tissue, TRAP5 of alveolar macrophages was detected in proximity to OPN to a higher degree than in normal lu...
Source: Frontiers in Immunology - December 8, 2022 Category: Allergy & Immunology Source Type: research